Multidisciplinary neurocutaneous syndrome clinics: a systematic review and institutional experience

TABLE 1.

Other described neurocutaneous clinics

TABLE 2.

General clinic data

TABLE 3.

Demographics and comorbidities characterized by diagnosis

TABLE 4.

Tumor management

TABLE 5.

Epilepsy management

Genetics

On the first visit, the geneticist completes or reviews a genetic questionnaire and family pedigree. Genetic testing, if not previously performed, is then generally offered to the patient and their family. During this stage of workup, it is not uncommon for family members to also be diagnosed within the clinic. Genetic counseling is also made available to patients at every clinic encounter to discuss disease progression, inheritance patterns, and reproductive questions. This is especially important as patients reach reproductive age and consider having children of their own.

Our review showed that 15 of 16 described clinics had genetics represented as a core component of their clinic team. Studies have shown long-term surveillance to be a vital component of neurocutaneous management.² In their cohort of VHL patients, Yoon et al.³ found the multidisciplinary model to be an effective means of providing long-term surveillance and genetic counseling. They reported that most visceral tumors in their clinic were asymptomatic and diagnosed incidentally on routine imaging surveillance.³ They also found that patients diagnosed with VHL who were not followed up in their clinic had significantly lower rates of ophthalmological examination, audiometry testing, and pheochromocytoma-related hormone tests.³ In a 10-year prospective follow-up study, Cnossen et al.⁴ found that the mean number of minor disease features was significantly higher in patients 6 years of age or younger who were later diagnosed with NF1. They advocated for routine surveillance and documentation of these features (macrocephaly, short stature, hypertelorism, and thorax abnormalities) from a young age as they serve as predictors of NF1 diagnosis.⁴

Neurology

Many of the manifestations of neurocutaneous disorders require medical treatment. Neurologists provide management for conditions such as headaches, epilepsy, and pain. In our patient cohort, roughly half of all patients complained of headache. Of the total clinic patient population, 33.5% had a history of at least one seizure. The majority (69%) were medically treated with a mean of 1.3 antiepileptic drugs. In epilepsy, early management is key to decrease of the chances of developing cognitive dysfunction or other psychiatric disorders.⁵

Infantile spasms seen in TSC are generally treated with vigabatrin as a first-line agent and adrenocorticotropic hormone as a second-line option. Neurologists also manage vascular malformations, and the use of antiplatelet therapy in SWS may be considered.

Neuro-Oncology

The role of the neuro-oncologist is invaluable for managing benign and malignant brain tumors. Oncologists and surgeons have the opportunity to collaborate and formulate the best management strategy for patients, be it surgery or chemoradiotherapy. Advances in molecularly targeted treatment and potential immunological treatment of these tumors continue to be studied for this purpose. One of the most commonly used pharmaceuticals is everolimus, a mechanistic target of rapamycin (mTOR) inhibitor. Studies have shown everolimus to be an effective option for inducing stabilization or shrinkage in recurrent or progressive NF1-associated low-grade glioma.⁶ Additionally, clinical trials have demonstrated that adjunctive everolimus is a well-tolerated option in pediatric patients with medically refractory epilepsy due to TSC, showing a sustained seizure reduction at 1 year.^7,8 MEK inhibitors have also been tested in clinical trials.^9,10 They were found to have a favorable profile and deemed safe in neurocognitive functioning in NF1 clinical trials.¹¹

Neurosurgery

Perhaps the most predominant roles for neurosurgical intervention in these patients include CNS tumors and refractory epilepsy. Other associated conditions that could potentially require intervention include Chiari malformation, tethered cord, scoliosis, vascular malformations, and hydrocephalus necessitating ventriculoperitoneal shunt placement.

Both brain and spinal tumors are frequently encountered in the neurocutaneous clinic (Table 3) and may require surgical intervention in addition to chemotherapy and/or radiation therapy. Studies from databases housed by multidisciplinary clinics have documented the rates of plexiform neurofibromas and other thoracic tumors causing spinal compression in NF1 within their own clinics.^12,13

Epilepsy is another common neurological manifestation of neurocutaneous disorders. One systematic review found the lifelong prevalence of epilepsy in NF1 to be 5.4%.¹⁴ This value is significantly higher in TSC, as tubers, hamartomas, subependymal giant cell astrocytomas, and epilepsy are hallmarks of the disorder. This patient population presents unique challenges in epilepsy treatment and has known indications for surgery and laser ablation.^15–22 SWS has also been shown to be associated with increased rates of drug-refractory epilepsy.²³

Although there is no known pathophysiological relationship between NF and tethered cord, there seems to be a correlation between the two. One study found the rate of tethered cord in NF patients to be as high as 13%.²⁴ In our cohort, this value was 6.5% and all of our patients underwent surgical correction.

Psychiatry

It is well known that neurocutaneous syndromes are associated with cognitive impairment and higher rates of concomitant psychiatric disorders. This is especially true of attention deficit hyperactivity disorder (ADHD), learning disabilities, behavioral problems, anxiety, and depression.²⁵ In our patient population, 74% of patients had ADHD and/or a learning disability, and 17% were diagnosed with anxiety and/or depression.

Psychologists screen for mental health diagnoses, problems with learning, neurocognitive deficits, family stressors, and health maintenance behaviors. They also provide psychoeducation and brief behavioral interventions related to mental health, school accommodations, and health maintenance behaviors, as well as referrals for counseling, psychiatry, and neuropsychological testing.

One well-studied area in neurocutaneous disorders is the mental health of adults living with TSC. Multiple studies have shown that these patients report a decreased quality of life and require continued monitoring into adulthood.^26–28

Physical Therapy

Physical therapy can greatly improve the quality of life and function of some patients. However, a standard of care has yet to be established in pediatric and adult patients.²⁹

Pertinent areas in which physical therapy can intervene are evaluating coordination and strength and identifying and treating gait abnormalities. Tillmann et al. described the experience of their multidisciplinary hospital team in managing transient hemiparesis in SWS, in which physical therapy played a vital role.²

Removing Barriers to Access

The convenience of seeing a multitude of specialists during one clinic visit is invaluable to patients and their families. This is particularly true for those who live in rural areas and states with few, large academic centers who travel long distances for these appointments. These centers often provide health services to a larger number of uninsured and low-income patients and have the opportunity to advocate for patient funding.³⁷

Clinics also play a role in the transition of care from childhood into adulthood for many patients.^38,39 Peron et al. described a TSC clinic model in which they house both pediatric and adult clinics.³⁹ When the patient transitions into adult care, administrative staff simply transfer records between the two clinics. Pediatric and adult staff meet every 4 months to discuss patients and make the process even more seamless.

Decreased Cancellation and No-Show Rates

The ability for patients to see many providers at one visit has increased our reach within the state. When reviewing general clinic data, cancellations were defined as notification by the patient or their care provider if they were unable to keep their scheduled appointment within 24 hours of the appointment time. "No-shows," or missed appointments, were defined as failure to keep the appointment with no prior notification. Our clinic had 4.3% and 4.1% cancellation and no-show rates, respectively. Even condensing these values into a combined cancellation and no-show rate (8.4%), this rate was much lower than those reported in previous studies of pediatric clinics, in which no-show rates have been reported to be as high as 26%.⁴⁰ Not only does this hinder patients from receiving necessary services, but it also comes at a cost to the healthcare system. One analysis of the lost costs of no-shows in a pediatric neurology clinic showed that annual losses were more than $250,000.⁴⁰

Social Support

It would be hard to overstate the impact of the relationships formed in the clinic. Connections are formed between patients, within families, and with patients and their providers. One specific way that multidisciplinary clinics have the opportunity to do this is through the family-centered care approach. This method implements the patient’s family in treatment and has been proven effective in improving healthcare services, particularly in treating chronic conditions in the pediatric and adolescent populations.⁴¹ Multidisciplinary clinics have also been shown to improve patient satisfaction and patient outcomes.⁴²

Guidelines and Protocols

The teams of experts who comprise multidisciplinary clinics are up to date on current guidelines and ever-evolving protocols of various syndromes.^43–47 Multidisciplinary meetings also occur in which providers meet to discuss, refine, and create protocols.^48,49

The multidisciplinary nature of clinics is especially useful in cases of dual diagnoses in which management must be further individualized. In our clinic, there have been cases of craniosynostosis, moyamoya, osteosarcoma, type 1 diabetes, and Klinefelter syndrome that have required additional care and discussion.

Academics and Research

There is ongoing research in various fields of neurocutaneous disorders. Large academic centers have an opportunity to contribute largely to this research, as they have a higher concentration of rare diseases and more academic funding. It is the hope of many that this continued research will lead to earlier patient referrals to multidisciplinary clinics, better pediatric-to-adult transition of care, and prolonged life expectancy.

Multidisciplinary centers have furthered academics by participating in numerous clinical trials and studies.^4,50,51 The formation of clinic databases has allowed centers to perform their own clinical trials and studies as well as to participate in national databases.⁵² Perhaps the best examples of these are the Neurofibromatosis Clinic Network and the Tuberous Sclerosis Alliance (TOSCA).^53–56

Scheduling Limitations

Our clinic sees patients twice a month. Each clinic is 4 hours in length. Typically, 6 to 8 patients are seen within one clinic. This limitation of volume does not allow for the scheduling of patients with less complex cases who are typically followed in individual clinics. Additional clinic time would provide more appointment slots. Our providers tend to see patients together or in tandem, rather than seeing them individually. This allows more patients to be seen in one clinic session.

Personnel Rotations

Consistent personnel at each clinic visit enables providers to establish rapport with patients and become familiar with patients and their families. However, personnel rotations sometimes become inevitable, which results in less knowledge regarding the patient and their care. In order to mitigate this, our clinic keeps a fixed staff.